Prevalence and burden of migraine in the United States: A systematic review.

BACKGROUND: This study reviewed migraine prevalence and disability gathered through epidemiologic survey studies in the United States conducted over the past three decades. We summarized these studies and evaluated changing patterns of disease prevalence and disability. METHODS: We conducted a systematic review of US studies addressing the prevalence, disability, and/or burden of migraine, including both episodic migraine (EM) and chronic migraine (CM). A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used in conjunction with the PubMed search engine. Eligible studies were published before February 2022, were conducted in the United States, included representative samples, and used a case definition of migraine based on the International Classification of Headache Disorders (ICHD). The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS). The MIDAS measures days lost due to migraine over 3 months in three domains and defines groups with moderate (Grade III) or severe disability (Grade IV) using cut-scores. RESULTS: Of the 1609 identified records, 26 publications from 11 US population-based studies met eligibility criteria. The prevalence of migraine in the population has remained relatively consistent for the past 30 years: ranging from 11.7% to 14.7% overall, 17.1% to 19.2% in women, and 5.6% to 7.2% in men in the studies reviewed. CM prevalence is 0.91% (1.3% among women and 0.5% of men) in adults and 0.8% in adolescents. The proportion of people with migraine and moderate-to-severe MIDAS disability (Grades III-IV), has trended upward across studies from 22.0% in 2005 to 39.0% in 2012, to 43.2% in 2016, and 42.4% in 2018. A consistently higher proportion of women were assigned MIDAS Grades III/IV relative to men. CONCLUSION: The prevalence of migraine in the United States has remained stable over the past three decades while migraine-related disability has increased. The disability trend could reflect changes in reporting, study methodology, social and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling, among other hypotheses. These issues merit further investigation.

Predictors of treatment-response to caffeine combination products, acetaminophen, acetylsalicylic acid (aspirin), and nonsteroidal anti-inflammatory drugs in acute treatment of episodic migraine.

OBJECTIVE: To identify predictors of acute treatment optimization for migraine with "over-the-counter" (OTC) or prescription nonsteroidal anti-inflammatory drugs (NSAIDs) as well as other widely used OTCs including acetaminophen, caffeine combination products (CCP), and acetylsalicylic acid (ASA, aspirin) among people with episodic migraine and to develop models that predict treatment response to each class of OTCs. BACKGROUND: Efficacy of acute OTC medications for migraine varies greatly. Identifying predictors of treatment response to particular classes of medication is a step toward evidence-based personalized therapy. METHODS: For this prediction model development study, we used data from 2224 participants from the American Migraine Prevalence and Prevention (AMPP) study who were aged ≥18 years, met criteria for migraine, had <15 monthly headache days, and reported being on monotherapy for acute migraine attacks with one of the following classes medications: CCP (N = 711), acetaminophen (N = 643), ASA (N = 110), and prescription or OTC NSAIDs (N = 760). The primary outcome measures of treatment optimization were adequate 2-h pain freedom (2hPF) and adequate 24-h pain relief (24hPR), which were defined by responses of half the time or more to the relevant items on the Migraine Treatment Optimization Questionnaire-6. RESULTS: The mean (SD) age of the participants was 46.2 (13.1) years, 79.4% (1765/2224) were female, 43.7% (972/2224) reported adequate 2hPF, and 46.1% (1025/2224) reported adequate 24hPR. Those taking CCP had better 2hPF and 24PR outcomes. For those taking NSAIDs, better outcomes were associated with lower average pain intensity (2hPF: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80-0.99; 24PR: OR 0.86, 95% CI 0.77-0.96), cutaneous allodynia (2hPF: OR 0.92, 95% CI 0.89-0.96; 24PR: OR 0.91, 95% CI 0.87-0.95), depressive symptoms (2hPF: OR 0.95, 95% CI 0.92-0.98; 24PR: OR 0.95, 95% CI 0.91-0.99), and Migraine Disability Assessment Scale (MIDAS) grade (2hPF: OR 0.76, 95% CI 0.64-0.90; 24PR: OR 0.79, 95% CI 0.65-0.95). Adequate 2hPF for those taking CCP was associated with male gender (OR 1.83, 95% CI 1.21-2.77), lower average pain intensity (OR 0.80, 95% CI 0.70-0.91), lower cutaneous allodynia (OR 0.94, 95% CI 0.90-0.97), and lower Migraine Symptom Severity Scale Score (MSSS; OR 0.91, 95% CI 0.86-0.97). Adequate 24hPR for those taking CCP was associated with lower average pain intensity (OR 0.85, 95% CI 0.75-0.96), lower cutaneous allodynia (OR 0.92, 95% CI 0.89-0.96), and lower MIDAS grade (OR 0.81, 95% CI 0.68-0.96). Participants who were married (OR 1.51, 95% CI 1.05-2.19), had lower average pain intensity (OR 0.79, 95% CI 0.70-0.89), lower MSSS (OR 0.93, 95% CI 0.88-0.99), less depression (OR 0.96, 95% CI 0.93-0.99), and lower MIDAS grade (OR 0.72, 95% CI 0.59-0.87) had adequate 2hPF after taking acetaminophen. Participants who were married (OR 1.50, 95% CI 1.02-2.21), had lower pain intensity (OR 0.78, 95% CI 0.69-0.88), less depression (OR 0.95, 95% CI 0.91-0.98) and lower MIDAS grade (OR 0.53, 95% CI 0.42-0.67) had higher 24hPR following use of acetaminophen. A lower MSSS was the only factor associated with higher 2hPF and 24PR after using ASA (OR 0.78, 95% CI 0.67-0.92 and OR 0.79, 95% CI 0.67-0.93). Predictive models had modest performance in identifying responders to each class of OTC. CONCLUSION: A large subgroup of people with migraine had an inadequate response to their usual acute OTC migraine treatment 2- and 24-h after dosing. These findings suggest a need to improve OTC treatment for some and to offer prescription acute medications for others. Predictive models identified several factors associated with better treatment-response in each OTC class. Selecting OTC treatment based on factors predictive of treatment optimization might improve patient outcomes.

Impact of monthly headache days on migraine-related quality of life: Results from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study.

OBJECTIVE: To characterize the direct impact of monthly headache days (MHDs) on health-related quality of life (HRQoL) in people with migraine and the potential mediating effects of anxiety, depression, and allodynia. BACKGROUND: Although the general relationship between increased migraine frequency (i.e., MHDs) and reduced HRQoL is well established, the degree to which reduced HRQoL is due to a direct effect of increased MHDs or attributable to mediating factors remains uncertain. METHODS: Cross-sectional baseline data from participants with migraine who completed the Core and Comorbidities/Endophenotypes modules in the 2012-2013 US Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a longitudinal web-based survey study, were analyzed. The potential contribution of depression, anxiety, and/or allodynia to the observed effects of MHDs on HRQoL as measured by the Migraine-Specific Quality-of-Life Questionnaire version 2.1 (MSQ) was evaluated. RESULTS: A total of 12,715 respondents were included in the analyses. The MSQ domain scores demonstrated progressive declines with increasing MHD categories (B = -1.23 to -0.60; p < 0.001). The observed HRQoL decrements associated with increasing MHDs were partially mediated by the presence of depression, anxiety, and allodynia. The MHD values predicted 24.0%-32.4% of the observed variation in the MSQ domains. Depression mediated 15.2%-24.3%, allodynia mediated 9.6%-16.1%, and anxiety mediated 2.3%-6.0% of the observed MHD effects on the MSQ. CONCLUSIONS: Increased MHD values were associated with lower MSQ scores; the impact of MHDs on the MSQ domain scores was partially mediated by the presence of depression, anxiety, and allodynia. MHDs remain the predominant driver of the MSQ variation; moreover, most of the variation in the MSQ remains unexplained by the variables we analyzed. Future longitudinal analyses and studies may help clarify the contribution of MHDs, comorbidities, and other factors to changes in HRQoL.

Pre- and post-headache phases of migraine: multi-country results from the CaMEO - International Study.

BACKGROUND: Individuals with migraine frequently experience pre- and post-headache symptoms. This analysis aimed to characterize the relative frequency and burden of pre- and post-headache symptoms in people with migraine using data collected through the Chronic Migraine Epidemiology and Outcomes - International Study. METHODS: This cross-sectional, observational, web-based survey was conducted in 2021-2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States. Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria were offered the opportunity to participate. Information collected included migraine-related disability, depression/anxiety symptoms, cutaneous allodynia, activity limitations, and acute treatment optimization. Respondents indicated how often they had pre- or post-headache symptoms using a 5-point scale, ranging from 0 to 4, with a rating of 2 or higher classified as a pre- or post-headache symptom case. Modeling was used to examine relationships with monthly headache days (MHDs) and activity limitations during pre-headache and post-headache phases. RESULTS: Among a total of 14,492 respondents, pre-headache symptoms were reported by 66.9%, while post-headache symptoms were reported by 60.2%. Both pre-headache and post-headache symptoms were reported by 49.5% of respondents, only pre-headache by 17.4%, only post-headache by 10.7%, and neither pre- nor post-headache symptoms by 22.4%. Compared with respondents who experienced only pre- or post-headache symptoms, respondents who experienced both pre- and post-headache symptoms had the highest rates of 4-7, 8-14, and ≥ 15 monthly headache days (23.1%, 14.1%, and 10.9%, respectively). Of respondents with both pre- and post-headache symptoms, 58.5% reported moderate-to-severe disability, 47.7% reported clinically significant symptoms of depression, 49.0% reported clinically significant symptoms of anxiety, and 63.8% reported cutaneous allodynia with headache (ASC-12). Moderate-to-severe activity limitations were reported during the pre-headache (29.5%) and post-headache phases (27.2%). For all outcomes modeled, after controlling for covariates, having pre-headache symptoms, post-headache symptoms, or both were associated with worse outcomes than having neither. CONCLUSIONS: Pre- and post-headache phases of migraine are common, carry unrecognized burden, and may be a target for treatment.

Predictive models for determining treatment response to nonprescription acute medications in migraine: Results from the American Migraine Prevalence and Prevention Study.

OBJECTIVE: To identify predictors of acute treatment response for nonprescription (over-the-counter [OTC]) medications among people with migraine and develop improved models for predicting treatment response. BACKGROUND: Pain freedom and sustained pain relief are important priorities in the acute treatment of migraine. OTC medications are widely used for migraine; however, it is not clear which treatment works best for each patient without going through the trial and error process. METHODS: A prediction model development study was completed using the 2006 American Migraine Prevalence and Prevention Study survey, from participants who were aged ≥18, met criteria and headache day frequency for episodic migraine, did not take prescription medication for migraine, and used ≥1 of the following acute migraine medication classes: acetaminophen, aspirin, NSAIDs, or caffeine containing combination products (CCP). Two items from the Migraine Treatment Optimization Questionnaire were used to evaluate treatment response, adequate 2-h pain freedom (2hPF) and 24-h pain relief (24hPR), which were defined by a response to treatment ≥half the time at 2 h and 24 h post treatment, respectively. We identified predictors of adequate treatment response and developed models to predict probability of treatment response to each medication class. RESULTS: The sample included 3852 participants (3038 [79.0%] females) with an average age of 45.0 years (SD = 12.8). Only 1602/3852 (41.6%) and 1718/3852 (44.6%) of the participants reported adequate 2hPF and 24hPR, respectively. Adequate treatment-response was significantly predicted by lower average headache pain intensity, less cutaneous allodynia, and lower depressive symptom scores. Lower migraine symptom severity was predictive of adequate 2hPF and fewer monthly headache days was predictive of adequate 24hPR. Among participants reporting OTC monotherapy (n = 2168, 56.3%) individuals taking CCP were more likely to have adequate 2hPF (OR = 1.55, 95% CI 1.23-1.95) and 24hPR (OR = 1.79, 95% CI 1.18-1.88) in comparison with those taking acetaminophen. Predictive models were modestly predictive of responders to OTC medications (c-statistics = 0.65; 95% CI 0.62-0.68). CONCLUSION: These results show that response to acute migraine treatments is not optimized in the majority of people with migraine treating with OTC medications. Predictive models can improve our ability to choose the best therapeutic option for individuals with episodic migraine and increase the proportion of patients with optimized response to treatments.

Barriers to care in episodic and chronic migraine: Results from the Chronic Migraine Epidemiology and Outcomes Study.

OBJECTIVE: To assess rates of and factors associated with traversing fundamental barriers to good medical outcomes and pharmacologic care in individuals with episodic migraine (EM) and chronic migraine (CM), including socioeconomic status and race. BACKGROUND: Barriers to good outcomes in migraine include the lack of appropriate medical consultation, failure to receive an accurate diagnosis, not being offered a regimen with acute and preventive pharmacologic treatments (if indicated), and not avoiding medication overuse. METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study was a longitudinal Internet-based survey. Respondents who met criteria for migraine consistent with the International Classification of Headache Disorders, 3rd edition, had a Migraine Disability Assessment score ≥ 6, and provided health insurance coverage status were included in this analysis. Successfully traversing each barrier to care and the effects of sociodemographic characteristics were examined. RESULTS: Among 16,789 respondents with migraine, 9184 (54.7%; EM: 7930; CM: 1254) were eligible. Current headache consultation was reported by 27.6% (2187/7930) of EM and 40.8% (512/1254) of CM respondents. Among consulters, 75.7% (1655/2187) with EM and 32.8% (168/512) with CM were accurately diagnosed. Among diagnosed consulters, 59.9% (992/1655) with EM and 54.2% (91/168) with CM reported minimally appropriate acute and preventive pharmacologic treatment. Among diagnosed and treated consulters, in the EM group 31.8% (315/992) and in the CM group 74.7% (68/91) met medication overuse criteria. Only 8.5% (677/7930) of EM and 1.8% (23/1254) of CM respondents traversed all four barriers. Higher income was positively associated with likelihood of traversing each barrier. Blacks and/or African Americans had higher rates of consultation than other racial groups. Blacks and/or African Americans and multiracial people had higher rates of acute medication overuse. CONCLUSIONS: Efforts to improve care should focus on increasing consultation and diagnosis rates, improving the delivery of all appropriate guideline-based treatment, and avoidance of medication overuse.

Demographics, Headache Features, and Comorbidity Profiles in Relation to Headache Frequency in People With Migraine: Results of the American Migraine Prevalence and Prevention (AMPP) Study.

BACKGROUND: Migraine is typically divided into 2 headache frequency denominated categories, episodic migraine (EM) and chronic migraine (CM). Characterizing more narrow headache day frequency groups may be of value for better understanding the broad range of migraine experience and making treatment decisions. OBJECTIVE: To characterize the impact and burden of migraine in 4 monthly headache day (MHD) categories. METHODS: Respondents to the American Migraine Prevalence and Prevention Study 2005 survey who met criteria for migraine were categorized into low frequency episodic migraine (LFEM) 0-3, moderate frequency episodic migraine (MFEM) 4-7, high frequency episodic migraine (HFEM) 8-14, and CM with ≥15 headache days per month. Data including sociodemographics, headache features and symptomology, comorbidities, cutaneous allodynia, and severe migraine-related disability were compared among groups. We combined the low- and medium-frequency EM groups (L/MFEM) and compared them with the HFEM group in 1 set of models and compared the HFEM and CM groups in a second set of models. Binary logistic regression, linear regression, and ordered logistic regression were used depending upon the variable type and adjusted for sociodemographics. RESULTS: Among 11,603 eligible respondents with migraine, 67.7% (7860/11,603) were categorized with LFEM, 17.7% (2051/11,603) with MFEM, 7.8% (898/11,603) with HFEM, and 6.8% (794/11,603) with CM. The mean age was 46 (SD 13.7), 80.2% (9301/11,603) were female, and 90.0% (10,187/11,323) were White, 6.9% were Black (784/11,323), and 3.1% (352/11,323) were identified as Other race(s). Individuals with HFEM differed from L/MFEM on a wide range of sociodemographic variables in the categories of headache features, disability, and comorbidities while few differences were found when modeling HFEM vs CM. In comparison with L/MFEM and HFEM, the HFEM group was more likely to have severe disability (P < .001 OR = 1.74 [1.42, 2.15]), chronic pain (P ≤ .007 OR = 1.35 [1.09, 1.69]), arthritis (P = .001 OR = 1.44 [1.15, 1.80]), high cholesterol (P = .005, OR = 1.37 [1.10, 1.70]), ulcers (P = .016, OR = 1.44 [1.07, 1.93]), and depression (Patient Health Questionnaire [PHQ-9]) (P < .001 OR = 1.50 [1.22, 1.84]). CONCLUSION: While rates of migraine symptoms, headache impact and disability, and comorbidities generally increased with increases in MHD frequency, respondents with HFEM and CM were remarkably similar on a broad range of variables including sociodemographics, disability/impact, and comorbidities. There were many more significant differences between the HFEM and L/MFEM groups on the same variables. Future work should use empirical strategies to identify naturally occurring groups and possibly reconsider the boundary between CM and HFEM.

The Effect of Psychiatric Comorbidities on Headache-Related Disability in Migraine: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: To examine the influences of depression and anxiety on headache-related disability in people with episodic migraine or chronic migraine. BACKGROUND: Depression and anxiety are common comorbidities in people with migraine, especially among those with chronic migraine. METHODS: This cross-sectional analysis of data from the longitudinal, internet-based Chronic Migraine Epidemiology and Outcomes Study assessed sociodemographic and headache features, and headache-related disability (Migraine Disability Assessment Scale). Four groups were defined based on scores from validated screeners for depression (9-item Patient Health Questionnaire) and anxiety (7-item Generalized Anxiety Disorder Scale): depression alone, anxiety alone, both, or neither. RESULTS: Respondents (N = 16,788) were predominantly women (74.4% [12,494/16,788]) and white (84.0% [14,044/16,788]); mean age was 41 years. Depression was more likely in persons with chronic migraine vs episodic migraine (56.6% [836/1476] vs 30.0% [4589/15,312]; P < .001), as were anxiety (48.4% [715/1476] vs 28.1% 4307/15,312]; P < .001) and coexisting depression and anxiety (42.0% [620/1476] vs 20.8% [3192/15,312]; P < .001). After controlling for headache frequency and other covariates, depression alone, and anxiety alone were associated with 56.0% (rate ratio [RR], 1.56; 95% confidence interval [CI], 1.46-1.66) and 39.0% (RR, 1.39; 95% CI, 1.30-1.50) increased risks of moderate/severe migraine-related disability (both P < .001), respectively; the combination had an even greater effect on risk of moderate/severe disability (79.0% increase; RR, 1.79; 95% CI, 1.71-1.87; P < .001). CONCLUSIONS: Depression alone and anxiety alone are associated with greater headache-related disability after controlling for sociodemographic and headache features. Coexisting depression and anxiety are more strongly associated with disability than either comorbidity in isolation. Interventions targeting depression and anxiety as well as migraine itself may improve headache-related disability in people with migraine.

Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study.

BACKGROUND: Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity. METHODS: The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine. Eligible migraine participants averaged ≥1 MHDs over the prior 3 months. Comorbidities "confirmed by a healthcare professional diagnosis" were endorsed by respondents from a list of 21 common cardiovascular, neurologic, psychiatric, sleep, respiratory, dermatologic, pain and medical comorbidities. Multivariable binary logistic regression calculated odds ratios (OR) and 95% confidence intervals for each condition between the two groups adjusting for sociodemographics. Modeling within the migraine cohort assessed rates of conditions as a function of headache pain intensity, MHD frequency, and their combination. RESULTS: Analyses included 15,133 people with migraine (73.0% women, 77.7% White, mean age 43 years) and 77,453 controls (46.4% women, 76.8% White, mean age 52 years). People with migraine were significantly (P < 0.001) more likely to report insomnia (OR 3.79 [3.6, 4.0]), depression (OR 3.18 [3.0, 3.3]), anxiety (OR 3.18 [3.0 3.3]), gastric ulcers/GI bleeding (OR 3.11 [2.8, 3.5]), angina (OR 2.64 [2.4, 3.0]) and epilepsy (OR 2.33 [2.0, 2.8]), among other conditions. Increasing headache pain intensity was associated with comorbidities related to inflammation (psoriasis, allergy), psychiatric disorders (depression, anxiety) and sleep conditions (insomnia). Increasing MHD frequency was associated with increased risk for nearly all conditions and most prominent among those with comorbid gastric ulcers/GI bleeding, diabetes, anxiety, depression, insomnia, asthma and allergies/hay fever. CONCLUSIONS: In regression models controlled for sociodemographic variables, all conditions studied were reported more often by those with migraine. Whether entered into the models separately or together, headache pain intensity and MHD frequency were associated with increased risk for many conditions. Future work is required to understand the causal sequence of relationships (direct causality, reverse causality, shared underlying predisposition), the potential confounding role of healthcare professional consultation and treatment, and potential detection bias.

Epidemiology of migraine in men: Results from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: To assess migraine epidemiology in men by examining gender differences in disease presentation, comorbidities, and prognosis. PATIENTS AND METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a longitudinal survey of US adults with migraine identified by web questionnaire. Data were stratified by gender, collected between September 2012-November 2013, and included sociodemographics, headache features, Migraine Disability Assessment, Migraine Symptom Severity Score, Allodynia Symptom Checklist, and comorbidities. Discrete time hazard models addressed 1-year likelihood of transition from episodic to chronic migraine headache frequency. RESULTS: Of the 16,789 migraine respondents, 4294 were men (25.6%). Compared to women, men were slightly older at onset of their headaches (mean 24.1 vs. 22.3 years) and had fewer headache days/month (4.3 vs. 5.3 days), slightly less severe attacks (Migraine Symptom Severity Score, 21.6 vs. 22.6), reduced frequencies of grade IV Migraine Disability Assessment scores (15.7% vs. 24.1%), allodynia (32.6% vs. 49.7%), chronic migraine (6.5% vs. 9.6%, each p < 0.001), and common comorbidities. Men were less likely to report consulting a doctor for their headaches and receiving a migraine diagnosis if they consulted. Men and women with episodic migraine had similar crude 1-year risk of chronic migraine onset. Controlling for known risk factors (i.e. depression, headache frequency, allodynia), men had greater likelihood of chronic migraine onset at 6, 9, and 12 months (each p < 0.05). CONCLUSIONS: Findings confirmed gender differences. Men with migraine generally have less severe attacks and disability and are less likely to receive a diagnosis than women with migraine. Prognostic factors may be better understood for women than men.

Predictors of allodynia in persons with migraine: Results from the Migraine in America Symptoms and Treatment (MAST) study.

BACKGROUND: Cutaneous allodynia is a common clinical feature of migraine that has been associated with reduced efficacy of acute migraine treatments and an increased risk of disease progression. OBJECTIVE: Identify factors associated with allodynia in a sample of adults with migraine. METHODS: An online survey panel was used to identify adults with migraine who averaged at least 1 monthly headache day over the previous 3 months. Data on sociodemographics, headache frequency, headache pain intensity, migraine symptom severity, medication use, depression and anxiety, and cutaneous allodynia (via the Allodynia Symptom Checklist) were obtained. Binary logistic modeling predicted the presence of allodynia. Odds ratios and 95% confidence intervals (CI) were calculated. RESULTS: In total, 15,133 individuals with migraine met the eligibility criteria. Mean age was 43.1 years, 73.0% were female, and 81.0% were Caucasian. Allodynia was present in 39.9%. The fully adjusted model, controlling for sociodemographics and headache features, demonstrated that allodynia was significantly associated with a higher migraine symptom severity score (odds ratio 1.17, confidence interval 1.15, 1.19) and more severe pain intensity (odds ratio 1.11, confidence interval 1.08, 1.14); probable depression and/or anxiety (odds ratio 1.83, confidence interval 1.67, 2.00); and overuse of acute medication (odds ratio 1.23, confidence interval 1.09, 1.38). A higher number of monthly headache days increased the likelihood of allodynia, but the effect was attenuated in the fully adjusted model. CONCLUSION: In a representative sample of US adults with migraine, there were significant associations between allodynia and headache frequency and intensity, anxiety and/or depression, symptom severity, and acute medication overuse.

Discontinuation of Acute Prescription Medication for Migraine: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: This analysis assessed migraine-related burden and treatment decisions in Chronic Migraine Epidemiology and Outcomes (CaMEO) Study survey respondents who stopped taking acute prescription medications for migraine. BACKGROUND: Migraine is a common yet underdiagnosed and undertreated neurological disease often associated with significant disability. Acute prescription medications are underused, in part because patients discontinue treatment. Rates and reasons for discontinuing acute prescription medications require exploration. METHODS: The CaMEO Study is a longitudinal, Internet-based survey that identified and followed people who met modified ICHD-3 migraine criteria. For this analysis, eligible respondents had used acute prescription medication for migraine in the past but no longer used or kept these treatments on hand (discontinued users). Respondents who reported discontinuing acute prescription treatment answered questions about length of time since last use and reasons for stopping. Reasons for discontinuing were thematically summarized. Monthly headache day frequency, Migraine Disability Assessment (MIDAS), Patient Health Questionnaire 9-item depression screener, Generalized Anxiety Disorder 7-item screener, and the 12-item Allodynia Symptom Checklist were also assessed. RESULTS: Of 13,624 respondents with migraine, 4840 (35.5%) had ever used acute prescription medications and 1719 (35.5%) of those were discontinued users. Discontinued users had a mean (SD) age of 42.1 (14) years, and 1348/1719 (78.4%) were female. Monthly headache frequency of 0-4 days was reported by 1073/1719 (62.4%) of respondents, 5-9 days by 322/1719 (18.7%), 10-14 days by 135/1719 (7.9%), and ≥15 days by 189/1719 (11.0%). Two-thirds (1160/1719 [67.5%]) of discontinued users reported a receiving migraine (or chronic migraine) diagnosis from a doctor or other health professional in the past. Although all had spoken to a doctor about their headaches, 1504/1719 (87.5%) had stopped having their headaches managed or treated by a doctor for at least 12 months. Only 1 in 5 discontinued users reported being able to work or function normally with a headache, and 717/1719 (41.7%) had moderate to severe disability (MIDAS). Among the most commonly reported reasons for prescription medication discontinuation were switching to non-prescription pain medication (782/1719 [45.5%]), as well as concerns about prescription medication efficacy (484/1719 [28.2%]) and tolerability (428/1719 [24.9%]). Nearly half of respondents who reported either efficacy or tolerability concerns had moderate to severe disability. CONCLUSIONS: People with migraine who discontinue acute prescription medication have a high level of unmet treatment need. The majority cannot work or function normally with headaches, with 646/1719 (37.6%) of discontinued users reporting 5 or more headache days per month.

Life With Migraine: Effects on Relationships, Career, and Finances From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: To assess the effects of migraine on important life domains and compare differences between respondents with episodic and chronic migraine and between sexes. BACKGROUND: Migraine is associated with a substantial personal and societal burden and can also affect the interpersonal dynamics, psychological health and well-being, and financial stability of the entire family of the person with migraine. METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a prospective, longitudinal, Web-based survey study undertaken between September 2012 and November 2013 in a systematic U.S. sample of people meeting modified International Classification of Headache Disorders, 3rd edition migraine criteria: 19,891 respondents were invited to complete the Family Burden Module, which assessed the perceived impact of migraine on family relationships and life, career and finances, and overall health. Respondents were stratified by episodic migraine (<15 headache days/month) and chronic migraine (≥15 headache days/month) and sex for comparisons. RESULTS: A total of 13,064 respondents (episodic migraine: 11,944 [91.4%]; chronic migraine: 1120 [8.6%]) provided valid data. Approximately 16.8% of respondents not currently in a romantic relationship (n = 536 of 3189) and 17.8% of those in a relationship but not living together (n = 236 of 1323) indicated that headaches had contributed to relationship problems. Of those in a relationship and living together (n = 8154), 3.2% reported that they chose not to have children, delayed having children or had fewer children because of migraine (n = 260; episodic migraine: n = 193 of 7446 [2.6%]; chronic migraine: n = 67 of 708 [9.5%]; P < .001). Of individuals responding to career/finance items (n = 13,061/13,036), 32.7% indicated that headaches negatively affected ≥1 career area (n = 4271; episodic migraine: n = 3617 of 11,942 [30.3%]; chronic migraine: n = 654 of 1119 [58.4%]), and 32.1% endorsed worry about long-term financial security due to migraine (n = 4180; episodic migraine: n = 3539 of 11,920 [29.7%]; chronic migraine: n = 641 of 1116 [57.4%]). CONCLUSIONS: Migraine can negatively affect many important aspects of life including marital, parenting, romantic and family relationships, career/financial achievement and stability, and overall health. Reported burden was consistently greater among those with chronic migraine than among people with episodic migraine; however, few differences were seen between the sexes.

Sleep Disorders Among People With Migraine: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVES: We examined the cross-sectional association of sleep apnea and indices of sleep quality with both episodic migraine (EM) and chronic migraine (CM). BACKGROUND: Sleep apnea and abnormal patterns of sleep, such as insomnia, were associated with migraine onset, severity, and progression in previous research. METHODS: The Chronic Migraine Epidemiology & Outcomes Study, a longitudinal study, used a series of web-based surveys to assess migraine symptoms, burden, and patterns of health care utilization. Quota sampling was used from September 2012 to November 2013 to generate a representative sample of the US population. Persons who screened positive for sleep apnea on the Berlin Questionnaire are said to be at "high risk" for sleep apnea. Respondents indicated if they believed that they had sleep apnea, if a physician had diagnosed it, and if and how they were treated. Other aspects of sleep quality were assessed using the Medical Outcomes Study (MOS) Sleep Measures. RESULTS: Of 12,810 eligible respondents with migraine and data on sleep, 11,699 with EM (91.3%) and 1111 with CM (8.7%) provided valid data for this analyses. According to the Berlin Questionnaire, 4739/12,810 (37.0%) were at "high risk" for sleep apnea, particularly persons with CM vs EM (575/1111 [51.8%] vs 4164/11,699 [35.6%]), men vs women (1431/3220 [44.4%] vs 3308/9590 [34.5%]), people with higher body mass index, and older people (all P < .001). Among respondents to the MOS Sleep Measures, persons with CM were more likely to report poor sleep quality than those with EM, including sleep disturbance (mean [SD] values: 53.2 [26.9] vs 37.9 [24.3]), snoring (38.0 [33.9] vs 31.0 [32.1]), shortness of breath (34.9 [29.8] vs 15.3 [20.6]), somnolence (44.1 [23.4] vs 32.2 [21.2]), and less likely to report sleep adequacy (34.0 [24.2] vs 39.2 [22.1]). CONCLUSIONS: Compared with respondents with EM, a larger proportion of those with CM were at "high risk" for sleep apnea and reported poor sleep quality. This reflects an association between CM vs EM and sleep apnea and poor sleep quality; the potential relationships are discussed.

Unmet Acute Treatment Needs From the 2017 Migraine in America Symptoms and Treatment Study.

OBJECTIVES: To characterize unmet treatment needs in a sample of Migraine in America Symptoms and Treatment (MAST) Study participants using oral, acute prescription migraine medications. BACKGROUND: The MAST Study is a 2017 study of US adults with migraine that profiles current treatment patterns and identifies and quantifies unmet treatment needs. METHODS: Cross-sectional data from an online survey of US adults meeting ICHD-3 beta criteria for migraine. For inclusion in this paper, respondents self-reported a history of 3 or more monthly headache days (MHDs) in the past 3 months and at least 1 MHD in the past 30 days, and current use of orally administered acute prescription medication for headache. Three domains of unmet need were identified: inadequate treatment response (ie, inadequate 2-hour pain freedom, recurrence within 24 hours of initial relief), demanding attack characteristics (rapid onset of attack, headache associated with sleep), and unique patient characteristics (opioid or barbiturate overuse, cardiovascular comorbidity). Sociodemographics, oral medication use, and coexisting conditions and symptoms (ie, level of treatment optimization, psychological symptoms, attack-related cutaneous allodynia, and migraine symptom severity) were assessed for each domain and by the number of unmet need domains. RESULTS: Overall, 15,133 respondents met inclusion criteria, 26.0% (3930/15,133) reported current use of oral acute prescription medication to treat headache. Eligible participants had a mean age of 45.0 years, 73.6% [2892/3930] were women and 81.1% [3186/3930]) were White. A total of 95.8% (3765/3930) of respondents had at least 1 unmet acute treatment need; 89.5% (3516/3930) reported demanding attack characteristics, 74.1% (2912/3930) reported inadequate treatment response, and 16.1% (634/3930) presented with unique patient characteristics. Common areas of unmet need were rapid headache onset (65.3% [2567/3930]), moderate to severe disability (55.6% [2187/3930]), inadequate 2-hours pain freedom (49.0% [1892/3930]), and headache recurrence within 24 hours (38.0% [1493/3930]). An increasing number of unmet treatment need domains was associated with worsening psychological symptoms, attack-related cutaneous allodynia and migraine symptom severity. CONCLUSION: Nearly all MAST Study respondents using acute oral prescription medications for migraine reported at least 1 unmet treatment need. As unmet needs increased, so did coexisting conditions and symptom severity.

Migraine in America Symptoms and Treatment (MAST) Study: Baseline Study Methods, Treatment Patterns, and Gender Differences.

OBJECTIVES: To summarize the baseline methods for the Migraine in America Symptoms and Treatment (MAST) Study and evaluate gender differences in sociodemographics and headache features; consultation and diagnosis patterns; and patterns of acute and preventive treatment use for migraine among study participants. BACKGROUND: The MAST Study is a longitudinal, internet-based panel study of symptoms, approaches to management, and unmet treatment needs among US adults with migraine. This analysis focuses on the initial cross-sectional survey, conducted beginning in 2016, and is intended to update results from earlier national epidemiologic surveys of people with migraine in the United States. METHODS: Respondents to the MAST Study were recruited from a US nationwide online research panel. Stratified random sampling identified a representative cohort of adults (aged ≥18 years). We administered a validated diagnostic screener based on modified ICHD-3 beta criteria to identify individuals with migraine averaging at least 1 monthly headache day (MHD) over the previous 3 months. A baseline assessment evaluated sociodemographic and headache features, patterns of consultation and diagnosis, and use of acute and preventive medications for migraine. Frequency data and chi-square contrasts (P < .05) were used to compare respondents based on gender. RESULTS: Baseline survey data (N = 95,821) identified 18,353 respondents who met criteria for migraine, including 15,133 (women n = 11,049, men n = 4084) reporting at least 1 MHD for the preceding 3 months. The mean age of the sample was 43.1 (13.6) years; 73.0% of respondents were women, and 81.0% were Caucasian. Compared with men, women were younger (46.1 vs 42.0 years; P < .001); had more MHDs (5.6 vs 5.3; P < .001); and were more likely to report moderate or severe headache-related disability (45.9% vs 35.8%; P < .001) and cutaneous allodynia (43.7% vs 29.5%; P < .001). The lifetime rate of medical consultation for headache was 79.8% overall and slightly higher in women than in men. Women were more likely than men to have been diagnosed with migraine (48.3% vs 38.8%, P < .001). While 95.1% of people with migraine currently used acute treatment, the majority (58.9%) used over-the-counter (OTC) drugs to the exclusion of prescription drugs, while 11.3% used exclusively prescription drugs, and 20.5% used both. Among acute prescription medication users, women were more likely than men to take triptans (17.7% vs 14.3%, P < .001), while men were more likely than women to take opioids (14.5% vs 9.2%, P < .001). Oral formulations were used predominately (92.7% of the medication users), but men were more likely to use nasal sprays (13.6% vs 9.4%, P < .001) and injectables (7.9% vs 3.4%, P <  .001). Men (14.5%) were also significantly more likely than women (10.4%) to be taking daily oral preventive medication (P < .001). CONCLUSIONS: The MAST Study identified a large sample of women and men with migraine from a sampling frame that broadly resembles the US population. Low participation rate increases the risk of response bias, however, comparisons with Census data and prior population studies for the demographic and headache characteristics of the current sample suggest that findings are generalizable to the population of people with migraine. Women had more MHDs than men, and they were more likely to report migraine-related disability and cutaneous allodynia. The lifetime consultation rate for headache was relatively high, but many with migraine symptoms reported never having received a diagnosis of migraine from a healthcare professional. Acute prescription and preventive migraine treatments are underused. Migraine persists as an underdiagnosed and undertreated public health problem in 2018, and there are many opportunities to improve the diagnosis and treatment of people with this painful, disabling condition.

Identifying Natural Subgroups of Migraine Based on Comorbidity and Concomitant Condition Profiles: Results of the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: To identify natural subgroups of people with migraine based on profiles of comorbidities and concomitant conditions, hereafter referred to as comorbidities. BACKGROUND: Migraine is a heterogeneous disease. Identifying natural subgroups (endophenotypes) may facilitate biological and genetic characterization and the development of personalized treatment. METHODS: The Chronic Migraine Epidemiology and Outcomes Study is a prospective web-based survey study designed to characterize the course of migraine and related comorbidities in a systematic US sample of people with migraine. Respondents were asked if they ever had a specific comorbidity and, if present, whether the comorbidity was confirmed/diagnosed by a "doctor"; 62 comorbidities were available for analysis. Latent class analysis (LCA) modeling determined the optimal number of classes and a parsimonious set of comorbidities. RESULTS: Of the 12,810 respondents with migraine, 11,837 reported ≥1 comorbidity and were included in this analysis. After statistical analysis and clinical judgment reduced the number of comorbidities, we selected an 8-class model based on 22 comorbidities. Each class had a distinct pattern summarized as follows: Class 1, Most Comorbidities; Class 2, Respiratory/Psychiatric; Class 3, Respiratory/Pain; Class 4, Respiratory; Class 5, Psychiatric; Class 6, Cardiovascular; Class 7, Pain; Class 8, Fewest Comorbidities. The distribution of individuals across models was variable, with one-third of respondents in Class 8 (Fewest Comorbidities) and <10% in Class 1 (Most Comorbidities). Demographic and headache characteristics, not used in assigning class membership, varied across classes. For example, comparing Class 1 (Most Comorbidities) and Class 8 (Fewest Comorbidities), Class 1 had a greater proportion of individuals with severe disability (Migraine Disability Assessment grade IV; 48.1% vs 22.3% of overall individuals) and higher rates of allodynia (67.6% vs 47.0%), medication overuse (36.4% vs 15.0%), chronic migraine (23.1% vs 9.1%), and aura (40.1% vs 28.8%). CONCLUSIONS: LCA modeling identified 8 natural subgroups of persons with migraine based on comorbidity profiles. These classes show differences in demographic and headache features not used to form the classes. Subsequent research will assess prognostic and biologic differences among the classes.

Adolescent Perspectives on the Burden of a Parent's Migraine: Results from the CaMEO Study.

OBJECTIVE: To assess the impact of parental migraine on adolescents (aged 13-21 years) living within the parental home from the adolescent's perspective. BACKGROUND: Family members are affected by their parent's migraine. We surveyed adolescents on the social, academic, and emotional effects of their parent's migraine. METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) study was a longitudinal Web-based study with cross-sectional modules designed to assess migraine symptoms, severity, frequency, and disability; migraine-related consulting practices, healthcare utilization, medication use, comorbid health conditions, and family related burden associated with migraine. The Family Burden Module (adolescent version; FBM-A) from the CaMEO study assessed parents with migraine and adolescent household members (dyads). Adolescents ranged in age from 13-21 years and were living at home with their parent. The initial FBM-A survey included 52 items covering five domains, which was refined and reduced by confirmatory factor analysis to 36 items covering four domains. Depression (9-item Patient Health Questionnaire) and anxiety (7-item Generalized Anxiety Disorder scale) were assessed. Item responses were stratified by parent migraine status (episodic migraine [EM], <15 headache days/month; chronic migraine [CM], ≥15 headache days/month). Frequencies of activities/events missed because of parental headache were categorized as ≥1 time or ≥4 times/previous 30 days. RESULTS: The sample included 1,411 parent-adolescent dyads (parent with EM, n = 1,243 [88.1%]; parent with CM, n = 168 [11.9%]). Burden due to a parent's migraine was reported in four domains based on 36 items including: Loss of Parental Support and Reverse Caregiving (5 items); Emotional Experience (13 items); Interference with School (4 items); and Missed Activities and Events (14 items). Across domains, perceived burden was greater for adolescents of parents with CM vs EM. Rates of moderate-to-severe anxiety symptoms were higher among adolescents of parents with CM (6.2 vs 11.3%, P = .01), while moderate-to-severe depression symptom rates were similar (5.5 vs 8.9%, P = .08). More adolescents of CM vs EM parents reported having a headache within the previous 3 months (P < .001). CONCLUSIONS: Parental migraine negatively impacts adolescent children, extending our understanding of the family burden of migraine and emphasizing the potential benefit to children of optimizing migraine care.

Factors associated with acute medication overuse in people with migraine: results from the 2017 migraine in America symptoms and treatment (MAST) study.

BACKGROUND: The MAST Study is a longitudinal, cross-sectional survey study of US adults with migraine. These analyses were conducted to estimate rates of acute medication overuse (AMO) and determine associations of AMO with individual and headache characteristics. METHODS: Eligible respondents had ICHD-3-beta migraine, reported ≥3 monthly headache days (MHDs) in the past 3 months, ≥1 MHD in the past 30 days, and currently took acute headache medication. AMO was defined according to ICHD-3-beta thresholds for monthly days of medication taking when diagnosing medication overuse headache. RESULTS: Eligible respondents (N = 13,649) had a mean age of 43.4 ± 13.6 years; most were female (72.9%) and Caucasian (81.9%). Altogether, 15.4% of respondents met criteria for AMO. Compared with those not overusing medications, respondents with AMO were significantly more likely to be taking triptans (31.3% vs 14.2%), opioids (23.8% vs 8.0%), barbiturates (7.8% vs 2.7%), and ergot alkaloids (3.1% vs 0.6%) and significantly less likely to be taking NSAIDs (63.3% vs 69.8%) (p < 0.001 for all comparisons). Respondents with AMO had significantly more MHDs (12.9 ± 8.6 vs 4.3 ± 4.3, p  <  0.001); higher migraine symptom severity (17.8 ± 2.7 vs 16.4 ± 3.0, p  <  0.001), higher pain intensity scores (7.4 vs 6.5, p  <  0.001); and higher rates of cutaneous allodynia (53.7% vs 37.5%, p  <  0.001). Adjusted for MHDs, the odds of AMO were increased by each additional year of age (OR 1.02, 95% CI 1.02, 1.03); being married (OR 1.19, 95% CI 1.06, 1.34); smoking (OR 1.54, 95% CI 1.31, 1.81); having psychological symptoms (OR 1.62, 95% CI 1.43, 1.83) or cutaneous allodynia (OR 1.22, 95% CI 1.08, 1.37); and greater migraine symptom severity (OR 1.06, 95% CI 1.04, 1.09) and pain intensity (OR 1.27, 95% CI 1.22, 1.32). Cutaneous allodynia increased the risk of AMO by 61% in males (OR 1.61, 95% CI 1.28, 2.03) but did not increase risk in females (OR 1.08, 95% CI 0.94, 1.25). CONCLUSIONS: AMO was present in 15% of respondents with migraine. AMO was associated with higher symptom severity scores, pain intensity, and rates of cutaneous allodynia. AMO was more likely in triptan, opioid, and barbiturate users but less likely in NSAID users. Cutaneous allodynia was associated with AMO in men but not women. This gender difference merits additional exploration.

Framingham-Based Cardiovascular Risk Estimates Among People With Episodic Migraine in the US Population: Results from the American Migraine Prevalence and Prevention (AMPP) Study.

BACKGROUND: Cardiovascular (CV) events, conditions, and procedures (ECPs) are common in persons with migraine and are a contraindication to triptan and ergot use. In a prior study, we estimated that there are 2.6 million American adults with episodic migraine (EM) who have had CV ECPs. However, the prior analysis did not assess persons with migraine without CV ECPs who are at high risk for a first cardiovascular disease (CVD) event. OBJECTIVES: To use the Framingham nonlaboratory CVD events risk equation to estimate the number of individuals with EM who are at elevated risk for a first CVD event in the next 10 years using data from the American Migraine Prevalence and Prevention Study, and then to extrapolate the findings to the US population to estimate the scope of people with EM for whom triptan and ergot therapies may be problematic. METHODS: Data from respondents to the 2009 American Migraine Prevalence and Prevention (AMPP) Study questionnaire aged ≥22 who met criteria and headache day frequency for EM were included in this cross-sectional analysis. Ten-year, first CVD event risk was calculated using the nonlaboratory Framingham CV disease risk score (FRS). Variables were collected via respondent self-report and included sex, age, height, and weight to calculate body mass index (BMI), smoking status, and the presence of hypertension and diabetes among other variables. Standard FRS cut scores of ≥21 for women and ≥16 for men were used, which indicate a 30% or greater risk of a first CVD event in the next 10 years. History of CV ECPs was collected via self-report of ever having the ECP and for events and conditions that were diagnosed by a physician. We applied rates of positive ECPs and rates of high FRS to age and sex stratified estimates of the number of people with EM in the US derived from 2015 US Census data to estimate rates of both in the population. RESULTS: The AMPP Study analysis sample included 5227 women and 1496 men with EM. Results showed that 69.5% of women and 73.4% of men had at least one CV risk factor from the FRS, 38.9% of women and 41.6% of men had ≥2 risk factors, and 18.6% of women and 19.1% of men had ≥3 risk factors. The proportion of women with high FRS was 0% for those aged 22-39, 0.8% (95%CI: 0.5-1.2%) among 40- to 59-year-olds and 15.2% (95% CI: 13.3-17.4%) among the ≥60 age group. For men, the corresponding proportions were 0, 7.3% (95% CI: 5.7-9.4%), and 53.0% (95% CI: 4.7-58.1%). Projecting to a national US sample, the number of persons with EM and high FRS was 403,000 for women and 510,000 for men. The proportion of women and men at high risk for future CV events based on a prior CV ECP, a high FRS or both increased with age from 20-39 (women 4.5%, men 4.2%), 40-59 (women 11.8%, men 18.6%), and ≥60 (women 31.2%, men 61.8%). An estimated 141,000 men aged 40-59 and 187,000 aged ≥60 and 34,000 women aged 40-59 and 181,000 women aged ≥60 in the US population with EM have not had a CV ECP but are at increased risk for a future CV event within the next 10 years based upon their FRS alone. CONCLUSION: Among people with EM in the US population, the number of women and men with relative contraindications to triptans and ergots based on a high FRS includes over 900,000 women and men. This includes more than half a million individuals with EM who have not had a prior CV ECP.